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(1) Background: The accurate diagnosis of esophageal strictures is quite critical for optimizing medical intervention. However, the diagnosis of suspicious malignant esophageal strictures with intact mucosa appearance and negative biopsy results is challenging. This study aimed to evaluate the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of suspicious esophageal strictures. (2) Methods: We retrospectively analyzed the cases with suspicious malignant esophageal strictures that underwent EUS-FNA, with or without rapid on-site evaluation (ROSE), in our hospital from April 2017 to September 2022. Their clinical manifestations, imaging examinations, gastroscopic examinations, EUS-FNA results, and therapeutic strategies were retrospectively recorded and analyzed. (3) Results: A total of 23 patients (15 male and 8 female) were enrolled in this study. Based on EUS-FNA results, 18 patients were diagnosed with malignancies, including 16 cases of primary esophageal cancer (13 squamous carcinomas and 3 adenocarcinomas), 1 case of mediastinal cancer, and 1 case of metastatic esophageal cancer; 1 case of tuberculosis was also confirmed by EUS-FNA. Among 4 cases of ambiguous diagnosis with EUS-FNA, 1 was diagnosed with an esophageal glomus tumor after surgical removal, and 2 patients survived for several years without medical intervention, which hinted at the possibility of benign esophageal strictures. No major complications, including bleeding or perforation, were observed. (4) Conclusions: EUS-FNA may serve as a safe and effective diagnostic tool in suspicious malignant esophageal strictures with accurate specimen acquisition, especially for biopsy-negative cases. [ABSTRACT FROM AUTHOR]

(1) Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for many kinds of tumors. However, whether ctDNA could be an accurate diagnostic biomarker in colorectal cancer (CRC) remains to be clarified. The aim of this study was to evaluate the diagnostic accuracy of ctDNA in CRC. (2) Methods: PubMed, Web of Science, and Cochrane databases were searched to identify studies reporting the use of ctDNA to screen and diagnose CRC, and all relevant studies published until October 2022 were enrolled for our analysis. These studies were divided into three primer subgroups: the subgroup of quantitative or qualitative analysis of ctDNA and the subgroup of septin9 (SEPT9) methylation assay. (3) Results: A total of 79 qualified articles with 25,240 subjects were incorporated into our meta-analysis. For quantitative studies, the combined sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR) were 0.723 (95% CI: 0.623–0.803), 0.920 (95% CI: 0.827–0.966), and 23.305 (95% CI: 9.378–57.906), respectively, yielding an AUC of 0.860. The corresponding values for qualitative studies were 0.610 (95% CI: 0.566–0.651), 0.891 (95% CI: 0.878–0.909), 12.569 (95% CI: 9.969–15.848), and 0.823, respectively. Detection of SEPT9 methylation depicted an AUC of 0.879, with an SEN of 0.679 (95% CI: 0.622–0.732), an SPE of 0.903 (95% CI: 0.878–0.923), and a DOR of 20.121 (95% CI:14.404–28.106), respectively. (4) Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for CRC screening and diagnosis. Specifically, quantitative analysis of ctDNA or qualitative analysis of SEPT9 methylation exhibited satisfying diagnostic efficiency. Larger sample studies are needed to further confirm our conclusions and to make the ctDNA approach more sensitive and specific. [ABSTRACT FROM AUTHOR]

Two oxidovanadium(V) complexes, [VOL1L] (1) and [VOL2L] (2) (L = ethyl maltolate), derived from the aroylhydrazones 4-bromo-N’-(2-hydroxy-5-methylbenzylidene)benzohydrazide (H2L1) and N’-(3,5-dibromo-2-hydroxybenzylidene)-4-methoxybenzohydrazide (H2L2), respectively, have been synthesized and characterized by elemental analysis, infrared and electronic spectroscopy. Structures of the complexes were further confirmed by single crystal X-ray determination. The V atoms in the complexes are coordinated by the ONO donor atoms of the aroylhydrazone ligand, OO donor atoms of the ethyl maltolate ligand, and one oxido O atom, forming octahedral coordination. The complexes function as effective olefin epoxidation catalysts with hydrogen peroxide as terminal oxidant and sodium hydrogen carbonate as a co-catalyst. [ABSTRACT FROM AUTHOR]

Fungi from unique environments exhibit special physiological characters and plenty of bioactive natural products. However, the recalcitrant genetics or poor transformation efficiencies prevent scientists from systematically studying molecular biological mechanisms and exploiting their metabolites. In this study, we targeted a guanophilic fungus Amphichorda guana LC5815 and developed a genetic transformation system. We firstly established an efficient protoplast preparing method by conditional optimization of sporulation and protoplast regeneration. The regeneration rate of the protoplast is up to about 34.6% with 0.8 M sucrose as the osmotic pressure stabilizer. To develop the genetic transformation, we used the polyethylene glycol-mediated protoplast transformation, and the testing gene AG04914 encoding a major facilitator superfamily transporter was deleted in strain LC5815, which proves the feasibility of this genetic manipulation system. Furthermore, a uridine/uracil auxotrophic strain was created by using a positive screening protocol with 5- fluoroorotic acid as a selective reagent. Finally, the genetic transformation system was successfully established in the guanophilic fungus strain LC5815, which lays the foundation for the molecular genetics research and will facilitate the exploitation of bioactive secondary metabolites in fungi. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the effects of two arbuscular mycorrhizal fungi (AMF), Funneliformis mosseae and Paraglomus occultum, on leaf water status, root morphology, root sugar accumulation, root abscisic acid (ABA) levels, root malondialdehyde (MDA) content, and root antioxidant enzyme activities in white clover ( Trifolium repens L.) exposed to well-watered (WW) and drought stress (DS) conditions. The results showed that root colonization by F. mosseae and P. occultum was significantly decreased by 7-week soil drought treatment. Under drought stress conditions, mycorrhizal fungal treatment considerably stimulated root total length, surface area and volume, as compared with non-mycorrhizal controls. In addition, inoculation with arbuscular mycorrhizal fungi also increased leaf relative water content and accelerated the accumulation of root glucose and fructose under drought stress. Mycorrhizal plants under drought stress registered higher activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) and ABA levels in roots, while lower MDA contents, relative to non-mycorrhizal plants. As a result, mycorrhiza-inoculated plants represented better physiological activities (e.g. antioxidant defense systems, root morphology, and sugar accumulation) than non-inoculated plants in response to soil drought, whilst P. occultum had superior effects than F. mosseae. [ABSTRACT FROM AUTHOR]

The transcription factor Woolly (Wo) and its downstream gene CycB2 have been shown to regulate trichome development in tomato (Solanum lycopersicum). It has been demonstrated that only the gain-of-function allele of Slwo (SlWo V , the Slwo woolly motif mutant allele) can increase the trichome density; however, it remains unclear why the two alleles function differently in trichome development. In this study, we used Nicotiana benthamiana as a model and cloned the homologues of Slwo and SlCycB2 (named Nbwo and NbCycB2). We also constructed a Nbwo gain-of-function allele with the same mutation site as SlWo V (named NbWo V ). We found that both Nbwo and NbWoV directly regulate NbCycB2 and their own expression by binding to the promoter of NbCycB2 and their own genomic sequences. As form of a feedback regulation, NbCycB2 negatively regulates trichome formation by repressing Nbwo activity at the protein level. We also found that mutations in the Nbwo woolly motif can prevent repression of NbWoV by NbCycB2, which results in a significant increase in the amount of active Nbwo proteins and in increases in trichome density and the number of branches. Our results reveal a novel reciprocal regulation mechanism between NbCycB2 and Nbwo during trichome formation in N. benthamiana. [ABSTRACT FROM AUTHOR]

A pair of new oxidovanadium(V) complexes, [VOL1L]TAO83;EtOH (1) and [VOL2L]TAO83;EtOH (2) (L = acetohydroxamate), derived from the aroylhydrazones N'-(5-bromo-2-hydroxybenzylidene)-4-methoxybenzohydrazide (H2L1) and N'-(5-bromo- 2-hydroxybenzylidene)-4-methylbenzohydrazide (H2L2), have been prepared and characterized by elemental analyses, FT-IR, 1H and 13C NMR spectroscopy and single-crystal structural X-ray diffraction. The complexes have octahedral structures in which the aroylhydrazone ligands behave as binegative donors. Single-crystal structure analyses reveal that the V centers are coordinated by the donor atoms of the aroylhydrazone ligands, the acetohydroxamate ligands and the oxido groups. Crystal structures of the complexes are stabilized by hydrogen bonds. The complexes function as effective olefin epoxidation catalysts. [ABSTRACT FROM AUTHOR]

Recently, we have reported a systematic study of photoinduced electron-transfer reactions in ionic liquid solvents using neutral and anionic electron donors and a series of cyano-substituted anthracene acceptors [Wu, B.; Maroncelli, M.; Castner, E. W., Jr.Photoinduced Bimolecular Electron Transfer in Ionic Liquids. J. Am. Chem. Soc.139, 2017, 14568]. Herein, we report complementary results for a cationic class of 1-alkyl-4-dimethylaminopyridinium electron donors. Reductive quenching of cyano-substituted anthracene fluorophores by these cationic quenchers is studied in solutions of acetonitrile and the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. Varying the length of the alkyl chain permits tuning of the quencher diffusivities in solution. The observed quenching kinetics are interpreted using a diffusion-reaction analysis. Together with results from the prior study, these results show that the intrinsic electron-transfer rate constant does not depend on the quencher charge in this family of reactions. [ABSTRACT FROM AUTHOR]

Background. The effect of achieved blood pressure (BP) on first stroke and renal function decline among hypertensive patients with mild to moderate chronic kidney disease (CKD) is still uncertain. Methods. In total, 3230 hypertensive patients with estimated glomerular filtration rate 30-60 mL/min/1.73 m2 and/or proteinuria were included in the present analyses. Eligible participants were randomly assigned to a daily treatment of a combined enalapril 10mg and folic acid 0.8mg tablet or an enalapril 10mg tablet alone. Participants were followed up every 3months. The study outcomes included first stroke and the progression of CKD. Results. The median antihypertensive treatment duration was 4.7 years. Compared with participants with a time-averaged ontreatment systolic blood pressure (SBP) of 135 to-140mmHg, the incidence of total first stroke [1.7% versus 3.3%; hazard ratio (HR), 0.51; 95% confidence interval (CI): 0.26-0.99] and ischemic stroke (1.3% versus 2.8%; HR, 0.46; 95% CI: 0.22-0.98) decreased significantly in those with a time-averaged SBP of-135mmHg. Furthermore, a time-averaged diastolic blood pressure (DBP) of-80mmHg, compared with a time-averaged DBP level of 80 to-90mmHg, was significantly related to a decreased risk of hemorrhagic stroke (0.2% versus 0.9%; HR, 0.18; 95% CI: 0.04-0.80). However, compared with participants with a time-averaged SBP of 135 to-140mmHg, a lower but non-significant trend of CKD progression was found in those with a time-averaged SBP of-130mmHg. Conclusions. A BP treatment level of-135/80mmHg, compared with a BP treatment level of 135-140/80-90mmHg, could lead to a decreased risk of first stroke in hypertensive patients with mild-to-moderate CKD. [ABSTRACT FROM AUTHOR]

In existing forecasting research papers support vector regression with chaotic mapping function and evolutionary algorithms have shown their advantages in terms of forecasting accuracy improvement. However, for classical particle swarm optimization (PSO) algorithms, trapping in local optima results in an earlier standstill of the particles and lost activities, thus, its core drawback is that eventually it produces low forecasting accuracy. To continue exploring possible improvements of the PSO algorithm, such as expanding the search space, this paper applies quantum mechanics to empower each particle to possess quantum behavior, to enlarge its search space, then, to improve the forecasting accuracy. This investigation presents a support vector regression (SVR)-based load forecasting model which hybridizes the chaotic mapping function and quantum particle swarm optimization algorithm with a support vector regression model, namely the SVRCQPSO (support vector regression with chaotic quantum particle swarm optimization) model, to achieve more accurate forecasting performance. Experimental results indicate that the proposed SVRCQPSO model achieves more accurate forecasting results than other alternatives. [ABSTRACT FROM AUTHOR]

A novel dioxidomolybdenum complex, [MoO2L], derived from the tridentate aroylhydrazone 2-amino-N'-(2-hydroxy- 3-methylbenzylidene)benzohydrazide (H2L), has been prepared and characterized by elemental analysis, FT-IR, 1H NMR, and single crystal structural X-ray diffraction. The complex has distorted square pyramidal structure in which the aroylhydrazone ligand behaves as a binegative donor, leaving the amino-N group uncoordinated towards the metal center. Single crystal structure analysis reveals that the Mo(VI) center is coordinated by the donor atoms of the binegative aroylhydrazone ligand and two oxido groups. Crystal structure of the complex is stabilized by hydrogen bonds. The complex functions as an effective olefin epoxidation catalyst with hydrogen peroxide as terminal oxidant and sodium hydrogen carbonate as a co-catalyst. [ABSTRACT FROM AUTHOR]

Background: Umbilical cord blood (UCB) is becoming an alternative cell source for hematopoietic stem cell transplantation (HSCT). However, umbilical cord blood transplantation (UCBT) has been severely limited by low and finite numbers of hematopoietic stem cells and their delayed engraftment. New strategies are needed to improve ex vivo expansion efficiency and in vivo haematopoietic recovery.Methods: We produced an endothelium-targeted soluble Notch ligand, the Delta-Serrate-Lag-2 (DSL) domain of human Delta-like 1 fused with a RGD motif (hD1R), and tested the effects of this protein on human umbilical cord blood hematopoietic stem and progenitor cell (UCB-HSPC) ex vivo and in vivo.Results: hD1R-mediated ex vivo expansion system was able to significantly increase the absolute number of UCB-HSPCs. The hD1R-expanded cells had the enhanced homing and maintained long-term hematopoietic stem cell repopulation capacity in the bone marrow of immunodeficient nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice. Moreover, systemic administration of hD1R promoted the in vivo regeneration of donor cells in recipient mice and accelerated hematopoietic recovery, particularly in settings wherein the HSPCs dose was limiting.Conclusions: Our results indicated that hD1R might be applied in improving hematopoietic recovery and HSC engraftment in human UCBT. [ABSTRACT FROM AUTHOR]

In this paper, we present a framework for the hybrid omnidirectional and perspective robot vision system. Based on the hybrid imaging geometry, a generalized stereo approach is developed via the construction of virtual cameras. It is then used to rectify the hybrid image pair using the perspective projection model. The proposed method not only simplifies the computation of epipolar geometry for the hybrid imaging system, but also facilitates the stereo matching between the heterogeneous image formation. Experimental results for both the synthetic data and real scene images have demonstrated the feasibility of our approach. [ABSTRACT FROM AUTHOR]

The Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae) is a major citrus pest spread around the world. It is also a vector of the bacterium 'Candidatus Liberibacter asiaticus', considered the cause of the fatal citrus disease huanglongbing (HLB). Insect ryanodine receptors (RyRs) are the primary target sites of diamide insecticides. In this study, full-length RyR cDNA from D. citri (named DcRyR) was isolated and identified. The 15,393 bp long open reading frame of DcRyR encoded a 5130 amino acid protein with a calculated molecular weight of 580,830 kDa. This protein had a high sequence identity (76–79%) with other insect homologs and a low sequence identity (43–46%) with mammals. An MIR domain, two RIH domains, three SPRY domains, four RyR repeat domains, an RIH-associated domain at the N-terminus, two consensus calcium-binding EF-hands, and six transmembrane domains were among the characteristics that DcRyR shared with insect and vertebrate RyRs. In expression analysis, the DcRyR gene displayed transcript abundance in all tissues and developmental stages as well as gene-differential and stage-specific patterns. In addition, diagnostic PCR experiments revealed that DcRyR had three potential alternative splice variants and that splicing events might have contributed to the various functions of DcRyR. However, diamide resistance-related amino acid residue mutations I4790M/K and G4946E were not found in DcRyR. These results can serve as the basis for further investigation into the target-based diamide pesticide resistance of D. citri. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) tumor is a serious disease with high mortality rates and morbidity rates worldwide. Chemotherapy is a key treatment for GI, however, systematic side effects and inevitable drug resistance complicate the situation. In the process of therapy, P-glycoprotein (P-gp) could remove chemotherapy drugs from cells, thus causing multi-drug resistance. Chemodynamic therapy (CDT) utilizing Fenton chemistry has been used for cancer therapy, along with various combination therapies. The reactive oxygen species produced by CDT could inhibit P-gp's efflux pump function, which reduce chemoagents excretion and reverse drug resistance. In the present study, we developed novel nanocrystals (Cu2O@Pt NCs) to overcome drug resistance by reducing mitochondria-derived ATP through chemo/CDT in GI cancer. Furthermore, in vivo results in tumor-bearing mice demonstrated that treatment with Cu2O@Pt NCs with CDT and chemotherapy could achieve the most effective antitumor therapeutic effect with the least amounts of adverse effects. As a result, Cu2O@Pt NCs could provide a promising strategy for chemo/CDT-synergistic therapy. [ABSTRACT FROM AUTHOR]

Background This study hopes to establish the timeframe for a safe return to driving under different speed conditions for patients after minimally invasive total knee arthroplasty and further explores how well various kinds of functional tests on knee performance can predict the patients' braking ability. Methods 14 patients with right knee osteoarthritis were included in the present study and instructed to perform three simulated driving tasks at preoperative, 2 weeks postoperative and 4 weeks postoperative. Results The results showed that the total braking time at 4 week postoperative has attained the preoperative level at the driving speed 50 and 70 km/hr but not at the driving speed 90 km/hr. It had significantly improving in knee reaction time and maximum isometric force at 4 weeks postoperative. Besides, there was a moderate to high correlation between the scores of the step counts and the total braking time. Conclusions Summary, it is recommended that driving may be resumed 4 weeks after a right knee replacement but had to drive at low or moderate speed and the best predictor of safety driving is step counts. [ABSTRACT FROM AUTHOR]

To overcome the continuous decline in its gross domestic product growth rate, China has advocated new and old kinetic energy conversion (NOKEC) as a policy for sustainable economic development in the post-COVID-19 era. The innovation drivers of NOKEC are the key to promoting sustainable economic development. However, the innovation drivers have various orientations, and their selection requires multiple-criteria decision-making (MCDM). This study proposes a modified Delphi method combined with the best–worst method (BWM) as a research framework for selecting and ranking innovation drivers. Our results show the validity of this integrated research framework on a case based in China in the post-COVID-19 era. The results reveal 21 innovation-driven factors of NOKEC with varying levels of relative importance. These results may provide a basis for policymakers and researchers with a useful further understanding of the importance and prioritizing of innovation drivers. In this study, BWM uses 4% fewer pairwise comparisons than AHP, and the consistency ratio is in the range of 0.00 to 0.24. [ABSTRACT FROM AUTHOR]

Thehydrological frequency analysis (HFA) is the foundation for the hydraulic engineering design and water resources management. Hydrological extreme observations or samples are the basis for HFA; the representativeness of a sample series to the population distribution is extremely important for the estimation reliability of the hydrological design value or quantile. However, for most of hydrological extreme data obtained in practical application, the size of the samples is usually small, for example, in China about 40~50 years. Generally, samples with small size cannot completely display the statistical properties of the population distribution, thus leading to uncertainties in the estimation of hydrological design values. In this paper, a new method based on bootstrap is put forward to analyze the impact of sampling uncertainty on the design value. By bootstrap resampling technique, a large number of bootstrap samples are constructed from the original flood extreme observations; the corresponding design value or quantile is estimated for each bootstrap sample, so that the sampling distribution of design value is constructed; based on the sampling distribution, the uncertainty of quantile estimation can be quantified. Compared with the conventional approach, this method provides not only the point estimation of a design value but also quantitative evaluation on uncertainties of the estimation. [ABSTRACT FROM AUTHOR]

Isotopes have played an important role in chemistry, biology, and medicine. For the last three decades, we have focused on the use of organoboron compounds as precursors to isotopically labeled physiologically active reagents. During that period, we have successfully developed methods for incorporating short- and long-lived isotopes of carbon, nitrogen, oxygen, and the halogens using a variety of reactive organoboron precursors. In addition, labeling strategies employing polymer-supported organoboron derivatives were developed. In this report, we present a short overview focused on the evolution of radiolabeling techniques based on boron chemistry. [ABSTRACT FROM AUTHOR]

Degenerate shoulder tendons display evidence of hypoxia. However tendons are relatively avascular and not considered to have high oxygen requirements and the vulnerability of tendon cells to hypoxia is unclear. Cultured human tenocytes were exposed to hypoxia and the cellular response detected using QPCR, Western blotting, viability, and ELISA assays. We find that tenocytes respond to hypoxia in vitro by activating classical HIF-1α-driven pathways. Total hypoxia caused significant tenocyte apoptosis. Transcription factors typically involved in hypoxic response, HIF-1α and FOXO3A, were upregulated. Hypoxia caused sustained upregulation of several proapoptotic proteins known to mediate hypoxia-induced apoptosis, such as Bnip3 and Nix, but others were unchanged although they were reportedly hypoxia-sensitive in other cell types. Antiapoptotic proteins Bcl2 and Bcl-xL were unchanged by hypoxia. Normal human tenocytes expressed all isoforms of the hypoxia-induced vascular growth factor VEGF except VEGF-D. Hypoxia markedly upregulated VEGF-A mRNA, followed by increased VEGF protein secretion. However treatment with VEGF did not improve tenocyte survival. As a protective strategy for tenocytes at risk of hypoxic death we added prosurvival growth factors insulin or platelet rich plasma (PRP). Both agents strongly protected tenocytes from hypoxia-induced death over 48 h, suggesting possible efficacy in the acute postrupture tendon or integrating graft. [ABSTRACT FROM AUTHOR]

We describe a new semantic descriptor for robots to recognize visual places. The descriptor integrates image features and color information via the hull census transform (HCT) and image histogram indexing. Our approach extracts the semantic description based on the convex hull points and statistical calculation. The color histograms are then formed by four indices and added to the descriptor. The semantic codebook consists of several places with many image descriptors. Finally, a one-versus-one (OVO) multi-class support vector machine (SVM) is used to model the places. The proposed technique is achieved by using a high-level cue integration scheme based on the learning information over the color and feature space to optimally combine the weighted cues. It is suitable for visual place recognition, particularly for the images captured by an omnidirectional camera. The experimental results show that the codebook with less vectors is as robust as most popular codebooks under varying environments. The performance is evaluated and compared with several state-of-the-art descriptors. [ABSTRACT FROM PUBLISHER]

. Purpose: To explore the effect of glucosamine (GlcN) on transforming growth factor (TGF)-β signalling and several processes involved in proliferative vitreoretinopathy (PVR). Methods: We evaluated the surface levels of TGF-β receptor and its binding of TGF-β in ARPE-19 cells. Release of cytokines and collagen, and expression of signalling intermediates were quantified. Migration was qualitatively and quantitatively examined. The morphology of cells undergoing PVR in vitro and in a mouse PVR model was observed. Results: Glucosamine reduced the surface levels of TGF-β receptor and the ability of ARPE-19 cells to bind TGF-β. In ARPE-19 cells, TGF-β1 plus epidermal growth factor (EGF) or TGF-β2 increased the expression of alpha-smooth muscle actin (α-SMA) and decreased the expression of zona occludens protein (ZO-1). Transforming growth factor-(β2) also caused the release of platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF) and type 1 collagen and increased the phosphorylation of SMAD2 and SMAD3. Platelet-derived growth factor and CTGF stimulated cell migration, and TGF-β2 stimulated wound closure, contraction of collagen and changes in cell morphology. Conclusions: Treatment with GlcN counteracted all of these effects, and its administration in the mouse model reduced the morphologic appearance of PVR. Glucosamine could inhibit the TGF-β signalling pathway in retinal pigment epithelium cells and several of the downstream events associated with epithelial-mesenchymal transition and PVR. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cells (hiPSCs) provide new possibilities for regenerative therapies. In order for this potential to be achieved, it is critical to efficiently monitor the differentiation of these hiPSCs into specific lineages. Here, we describe a lentiviral reporter vector sensitive to specific microRNAs (miRNA) to show that a single vector bearing multiple miRNA target sequences conjugated to different reporters can be used to monitor hiPSC formation and subsequent differentiation from human fetal fibroblasts (HFFs). The reporter vector encodes EGFP conjugated to the targets of human embryonic stem cell (hESC) specific miRNAs (miR-302a and miR-302d) and mCherry conjugated to the targets of differentiated cells specific miRNAs (miR-142-3p, miR-155, and miR-223). The vector was used to track reprogramming of HFF to iPSC. HFFs co-transduced with this reporter vector and vectors encoding 4 reprogramming factors (OCT4, SOX2, KLF4 and cMYC) were mostly positive for EGFP (67%) at an early stage of hiPSC formation. EGFP expression gradually disappeared and mCherry expression increased indicating less miRNAs specific to differentiated cells and expression of miRNAs specific to hESCs. Upon differentiation of the hiPSC into embryoid bodies, a large fraction of these hiPSCs regained EGFP expression and some of those cells became single positive for EGFP. Further differentiation into neural lineages showed distinct structures demarcated by either EGFP or mCherry expression. These findings demonstrate that a miRNA dependent reporter vector can be a useful tool to monitor living cells during reprogramming of hiPSC and subsequent differentiation to lineage specific cells. [ABSTRACT FROM AUTHOR]

Steady-state absorption and emission and femtosecond time-resolved emission spectroscopy of two benzylidene malononitriles, 2-[4-(dimethylamino)benzylidene])malononitrile (DMN) and julolidinemalononitrile (JDMN), are reported in a variety of room-temperature solvents. Solvatochromic shifts of these molecules are consistent with dielectric continuum descriptions and an S1−S0dipole moment change of 8.5 D. Time-resolved spectra show modest dynamic Stokes shifts of ∼1000 cm−1occurring independently of fluorescence decay, which takes place in 0.5−5 ps in most room-temperature solvents. Absorption transition moments and fluorescence decay times are used to determine radiative rate constants: krad= 0.32 ± 0.02 ns−1in DMN and 0.28 ± 0.02 ns−1in JDMN, assumed to be independent of solvent. Quantum yield data together with these radiative rates provide the reaction rate constants krxnassociated with the internal conversion process of these molecules in 33 representative solvents at 298 K and in several solvents as functions of temperature. Reaction rates of JDMN are systematically lower than those of DMN by a factor of 2.0. Values of krxnin series of homologous solvents or in a single solvent at different temperatures are correlated to solvent viscosity η and temperature Tin the manner krxn/T∝ η−pwith exponents 0.2 ≤ p≤ 0.8. Solvent polarity appears to influence these reactions such that for a given viscosity reaction in high polarity solvents is significantly slower than in nonpolar solvents. However, this conclusion is predicated on the assumption that reactive friction is identical in solvents of the same viscosity, which is unlikely to be quantitatively correct. The observed reaction rates and their solvent dependence are discussed in terms of isomerization about the CC bond occurring on a shelf-like potential. [ABSTRACT FROM AUTHOR]

We recently developed a novel targeting Sindbis virus envelope pseudotyped lentiviral vector, 2.2ZZ, which acquires specific transduction capacity by antibody conjugation and binding with specific antigens on the surface of targeted cells. Here we characterize the virological properties of this vector by examining its targeting to CD4 antigen. Our results show that entry is dependent on CD4 cell surface density and occurs via the clathrin-mediated endocytic pathway. These findings provide insight into the mechanism of infection by a new viral vector with combined properties of Sindbis virus and lentiviruses and infectivity conferred by monoclonal antibody-ligand interactions. [ABSTRACT FROM AUTHOR]

AbstractIt is well recognized that brain death starts to occur just 4–6 min after cardiac arrest, and few attempts at resuscitation succeed after 10 min of severe cerebral ischemia and anoxia. We sought to determine the therapeutic window of selective cerebral profound hypothermia of primates following severe cerebral ischemia in primates. Fourteen rhesus monkeys with severe cerebral ischemia were divided into four groups: normothermia (n = 3); profound hypothermia I (n = 4), with cooling initiated 10 min after ischemia; profound hypothermia II (n = 4), with cooling initiated 15 min after ischemia; and profound hypothermia III (n = 3), with cooling initiated 20 min after ischemia. Severe cerebral ischemia was induced by clamping both the internal and external carotid arteries, as well as the internal and external jugular veins. Profound cerebral hypothermia (15.8° ± 0.9°C) was achieved and maintained for 60 min, and the animals were then re-warmed gradually. All four animals in hypothermia group I survived without any neurological deficits. Only 1 animal survived and 3 animals died in hypothermia group II. All 4 animals died in both hypothermia group III and the normothermia group. Neurological functions were normal in all surviving animals, and MRI scans showed no cerebral infarction in these animals. Microscopic examination showed no injured neurons in the hippocampus and cerebral cortex of the surviving animals, and showed that the heart, lung, liver, and kidneys were normal in these animals. Our data indicate that post-ischemic profound cerebral hypothermia provided significant cerebral protection with no systemic complications, and that the effective therapeutic window is more than 10 min, but less than 15 min, after severe cerebral ischemia. [ABSTRACT FROM AUTHOR]

Abstract: The use of organoborane intermediates for radiohalogenations is briefly reviewed. The synthesis of an iodine-123 labeled curcumin derivative using a newly developed radio-iodination technique is reported. [Copyright &y& Elsevier]

A boron trihalide mediated alkyne-aldehyde coupling reaction leading to stereodefined 1,3,5-triaryl-l,5- dihalo-1,4-pentadienes is described. The study led to the discovery of a direct substitution of hydroxyl groups by stereodefined alkenyl moieties using alkenylboron dihalides. During the investigation, it was also discovered that, at low temperatures, the reaction of BCI3 with alkynes produces monovinylboron dichioride rather than the reported divinylboron chloride. A modified reaction mechanism for the boron trichloride mediated alkyne-aldehyde coupling reaction is now proposed. The reaction temperature and mode of addition have been found to have dramatic affects on the stereochemistry of the diene products. [ABSTRACT FROM AUTHOR]

In this study, the problem of a planar blast wave in a duct with a sudden expansion is considered. An incident blast wave that contains two shock waves is arranged so that one pair of vortex rings induced by the first shock wave interacts with the second shock wave of the blast wave and with the reflected shock associated with the first shock wave. A high-resolution Euler/Navier-Stokes soiver using a fifth-order weighted essentially nonoscillation scheme is employed to investigate the problem. After the Euler/Navier-Stokes solver is validated to be reasonably accurate, the flow fields induced by the shock/vortex interactions are investigated by computational shadowgraph and computational schlieren techniques. It is found that the trajectories formed by major ring-vortex centers may be different case by case, depending on the arrival time sequence of the second shock wave and the reflected shock wave. In particular, a third vortex ring may be developed, causing the trajectory's turn at some critical time in viscous-flow models. Because of viscous dissipation, consequently stronger vortex-ring strength predicted by the inviscid-flow model than that for the viscous-flow model can result in 14-32% lower pressures at the major ring-vortex centers in the inviscid flow compared with the turbulent flow during the time interval investigated for case A, and 20-32% for case B, and 21-38% for case C. Because of the boundary layer development along the duct wall after the sudden expansion, the reflection type of the first shock wave is changed from a regular reflection in the inviscid-flow case to a single Mach reflection that directly affects the arrival time of the reflected shock wave at the sharp corner. Moreover, the mechanism of the vortex ring formation based on the inviscid-flow model is analyzed. It is found that the term due to the dilation effect also plays a more important role in vorticity generation than the baroclinic term. [ABSTRACT FROM AUTHOR]

BACKGROUND: Because metallothionein (MT) is a metal-binding protein that protects against metal intoxication, it could be a biomarker for individual sensitivity to metal toxicity. OBJECTIVE: We assessed the use of bloodborne MT transcript as a reflection of tissue MT levels and examined the potential role of MT in arsenic toxicity in an environmentally exposed human population. METHOD: Rodents were treated with zinc or nonmetallic MT inducers for 4 days, and the blood and tissues were collected for MT transcript analysis by real-time reverse transcriptase--polymerase chain reaction and MT protein determination by the cadmium--hemoglobin assay. Blood and buccal cell samples were collected from arsenicosis patients and healthy subjects residing in Guizhou, China, and total RNA was isolated for MT transcript analysis. RESULTS: There was a positive correlation between blood MT-1 and MT-2 transcripts and corresponding hepatic or renal MT transcript levels in rats and mice. Furthermore, there was a positive correlation between blood MT-1 and MT-2 transcript and tissue MT protein levels in these animals. A positive correlation also occurred between human blood MT and buccal cell MT transcript levels. MT-1A and MT-2A were the major isoform transcripts in human blood and buccal cells, and significantly lower MT levels were seen in arsenicosis patients compared with healthy subjects. CONCLUSIONS: Blood MT transcript appears to be a useful biomarker of tissue MT levels. Arsenicosis patients in Guizhou show significantly lower MT transcript levels in blood, which may have predisposed this population to arsenic intoxication. [ABSTRACT FROM AUTHOR]

MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that mir-21 is overexpressed in tumor tissues compared with the matched normal tissues. Moreover, suppression of mir-21 by antisense oligonucleotides inhibits tumor cell growth both in vitro and in vivo. However, it remains largely unclear as to how mir-21 affects tumor growth, because our understanding of mir-21 targets is limited. In this study, we performed two-dimensional differentiation in-gel electrophoresis of tumors treated with anti-mir-21 and identified the tumor suppressor tropomyosin 1 (TPM1) as a potential mir-21 target. In agreement with this, there is a putative mir-21 binding site at the 3′-untranslated region (3′-UTR) of TPM1 variants V1 and V5. Thus, we cloned the 3′-UTR of TPM1 into a luciferase reporter and found that although mir-21 down-regulated the luciferase activity, anti-mir-21 up-regulated it. Moreover, deletion of the mir-21 binding site abolished the effect of mir-21 on the luciferase activity, suggesting that this mir-21 binding site is critical. Western blot with the cloned TPM1-V1 plus the 3′-UTR indicated that TPM1 protein level was also regulated by mir-21, whereas real-time quantitative reverse transcription-PCR revealed no difference at the mRNA level, suggesting translational regulation. Finally, overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchor- age-independent growth. Thus, down-regulation of TPM1 by mir-21 may explain, at least in part, why suppression of mir-21 can inhibit tumor growth, further supporting the notion that mir-21 functions as an oncogene. [ABSTRACT FROM AUTHOR]

A new unusual pigment with a novel carbon framework named selaginellin (1) was isolated from the acetone extract of Selaginella sinensis, and its methoxy derivative (1a) was synthesized. Both selaginellin 1 and la are racemic com- pounds. The structure of selaginellin 1 was established as (R,S)-4-[(4′-hydroxy-4-(hydroxymethyl)-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylenel-2,5-cyclohexadien-1-one and la as (R,S)-4-[(4′-methoxy-4-(methoxymethyl)-3-((4-methoxyphenyl)ethynyl)biphenyl-2-yl)(4-methoxyphenyl)methylenel-2,5-cyclohexadien-1-one by the analysis of one- and two-dimensional NMR data, HR-ESIMS, El-MS. IR, UV, CD, and single-crystal X-ray experiments, and the mechanism of their color change according to different pH values and fluorescent properties was studied. [ABSTRACT FROM AUTHOR]

Recent progress has been made on the role of oncoproteins c-Ski and related SnoN in the control of cellular transformation. c-Ski/SnoN potently repress transforming growth factor-α (TGF-β) antiproliferative signaling through physical interaction with signal transducers called Smads. Overexpression of c-Ski/SnoN also induces skeletal muscle differentiation, but how c-Ski/SnoN function in myogenesis is largely unknown. During our investigation on the role of sumoylation in TGF-β signaling, we inadvertently found that SnoN is modified by small ubiquitin-like modifier-1 (SUMO-1). Here, we biochemically characterize SnoN sumoylation in detail and report the physiological function of the modification. Sumoylation occurs primarily at lysine 50 (Lys-50). PIAS1 and PIASx proteins physically interact with SnoN to stimulate its sumoylation, thus serving as SUMO-protein isopeptide ligases (E3) for SnoN sumoylation. SnoN sumoylation does not alter its metabolic stability or its ability to repress TGF-β signaling. Notably, loss of sumoylation in the Lys-50 site (via a Lys-to-Arg point mutation) potently activates muscle-specific gene expression and enhances myotube formation. Our study suggests a novel role for SUMO modification in the regulation of myogenic differentiation. [ABSTRACT FROM AUTHOR]

The problem of planar reflected-shock/spiral-vortex interactions near an open-ended duct is considered. The reflected shock is formed after exiting the duct and impinging on a vertical wall that is located downstream of the duct. Two cases associated with the shock diffraction around the duct exit are investigated for understanding the detailed flow structure and acoustic waves due to the reflected shock/spiral-vortex interaction. One is a 90-deg diffraction; the other is a 180-deg diffraction. An Euler solver with a high-resolution scheme of weighted essential nonoscillation is used to study these complicated flow problems. The Euler solver is validated to be reasonably accurate by comparing the computed solution with experimental data. For the study of reflected-shock/spiral-vortex interactions, the techniques of computational shadowgraph, computational schlieren image, and computational interferometry are used. Detailed flow structures of reflected shock/vortex interactions are reported for different incident shock Mach numbers. An interesting result of stagnant reflected shock waves downstream of the duct is found for an incident shock Mach number equal to or greater than 1.4. For the incident shock Mach number below this critical value, the reflected shock Rt will eventually enter the duct. The mechanism for the formation of acoustic waves generated by reflected-shock/vortex interactions is analyzed. [ABSTRACT FROM AUTHOR]

A novel boronated aminocyclobutanecarboxylic acid (1) was synthesized for potential use in boron neutron capture therapy. Starting from the readily available 3-(bromomethyl)cyclobutanone ketal (4), several synthetic routes to I were evaluated. After several unsuccessful attempts with traditional synthetic methods, a novel synthetic strategy to generate the new boronated cyclic amino acid was developed. The tolerance of the hydantoin group to the selenoxide elimination reaction conditions in the preparation of alkenyl compound 7 proved to be the key step in the new strategy. [ABSTRACT FROM AUTHOR]

The tumor suppressor, Smad4/DPC4, is a common signal transducer in transforming growth factor-β (TGF-β) signaling. In this study, we demonstrated that the protein inhibitor of activated STAT1 (PIAS1) regulates the signaling potential of Smad4 through a sumoylation-dependent mechanism. PIAS1 was shown to be an E3 ligase for Smad4 sumoylation in vitro and in vivo. PIAS1 physically interacted with Smad4 in a TGF-β-inducible manner. A minimal SUMO E3 ligase domain and Smad4binding domain were defined on PIAS1 protein. The RING finger domain of PIAS1 was essential for its E3 ligase function. Although PIAS1 enhanced the Smad4dependent transcriptional activation of TGF-β signaling, a mutant lacking the RING domain inhibited the sumoylation of Smad4 in a dominant negative manner and, as a result, abolished the transcriptional response of TGF-β. These data demonstrate that PIAS1 protein positively modulates TGF-β responses as a SUMO E3 ligase for Smad4. [ABSTRACT FROM AUTHOR]

We have previously shown that transactivation-proficient hepatitis virus B X protein (HBx) protects Hep 3B cells from transforming growth factor-β (TGF-β)-induced apoptosis via activation of the phosphatidylinosiroi 3-kinase (PI 3-kinase)/Akt signaling pathway. This work further investigated how HBx activates PI 3-kinase. Src activity was elevated in Hep 3B cells following expression of transactivation-proficient HBx or HBxGFP fusion proteins. The Src family kinase inhibitor PP2 and C-terminal Src kinase (Csk) both alleviated HBx-mediated PI 3-kinase activation and protection from TGF-β-induced apoptosis. Therefore, HBx actirated a survival signal by linking Src to PI 3-kinase. Systemic subcellular fractionation and membrane flotation assays indicated that ∼1.5% of ectopically expressed HBxGFP was associated with periplasmic membrane where Src was located. However, neither nucleustargeted nor periplasmic membrane-targeted HBxGFP was able to upregulate Src activity or to augment PI 3-kinase survival signaling pathway. [ABSTRACT FROM AUTHOR]

Tumor suppressor Smad4/DPC4 is a central intracellular signal transducer for transforming growth factor-β (TGF-β) signaling. We recently reported that transcriptional potential of Smad4 was regulated by SUMOylation in transfected HeLa cells (1), but the precise mechanism and function of Smad4 SUMOylation in TGF-β signaling remain to be elucidated. Here, we describe the regulation of TGF-β signaling by SUMOylation through the control of Smad4 metabolic stability and subcellular localization. We found that SUMO-1 overexpression strongly increases Smad4 levels, while inhibition of SUMOylation by small interfering RNA (siRNA)-mediated knockdown of the E2 enzyme Ubc9 reduces endogenous Smad4 levels. Concomitantly, SUMO-1 overexpression enhances and Ubc9 knockdown reduces levels of intranuclear Smad4, growth inhibitory response, as well as transcriptional responses to TGF-β. Comparison of wild type and mutant forms of Smad4 for SUMOylation, ubiquitination, and half-life allows the conclusion that SUMO-1 modification serves to protect Smad4 from ubiquitin-dependent degradation and consequently enhances the growth inhibitory and transcriptional responses of Smad4. [ABSTRACT FROM AUTHOR]

Investigates the activation of transforming growth factor-beta (TGF-beta) signaling through the involvement of small ubiquitin-like modifier-1 modification of tumor suppressor Smad4/DPC4. Association between the MH1 domain of Smad4 with a carrier protein conjugating enzyme; Observation on the mutation ability of lysine residues in altering conjugation; Enhancement of TGF-beta-induced transcription process.

Interleukin-6 (IL-6) has received particular attention in the pathogenesis of cervical cancer, although the underlying mechanism remains elusive. This study revealed that IL-6 promotes in vivo tumor growth of human cervical cancer C33A cells, but does not substantially alter their in vitro growth kinetics. The in vivo angiogenic assays showed that IL-6 increases angiogenic activity in human cervical cancer cells, an effect that is specifically associated with upregulation of vascular endothelial growth factor (VEGF). Also, using anti-VEGF antibody to block VEGF function significantly inhibited IL-6-mediated angiogenesis and tumor growth in nude mice, strongly supporting the critical role of VEGF in the IL-6-mediated cervical tumorigenesis. Accordingly, the signaling pathway downstream of IL-6/IL-6R responsible for the regulation of VEGF was investigated. Notably, pharmacological inhibition of PI3-K or MAPK failed to inhibit IL-6-mediated transcriptional upregulation of VEGF. Meanwhile, blocking STAT3 pathway with dominant-negative mutant STAT3D effectively abolished IL-6-induced VEGF mRNA. In transient transfections, a luciferase reporter construct containing the full-length 1.5-kb VEGF promoter or a 1.2-kb fragment lacking the known hypoxic-response element also exhibited the same degree of response to IL-6. Additionally, transient transfection of STAT3D downregulated the 1.2-kb VEGF promoter luciferase reporter stimulated by IL-6. Based on the above phenomenon combined with the concomitant increased tumor expression of IL-6 and VEGF in cervical cancer tissues, we conclude that IL-6 may promote cervical tumorigenesis by activating VEGF-mediated angiogenesis via a STAT3 pathway.Oncogene (2003) 22, 1517-1527. doi:10.1038/sj.onc.1206226 [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6), a multifunctional cytokine, has recently been implicated in human cervical cancer, though the mechanism remains elusive. This study demonstrates that the anti-apoptotic protein Mcl-1 and IL-6 was concomitantly expressed in human cervical cancer tissues and cell lines, but not in normal cervix tissues. Upon IL-6 treatment, Mcl-1, but not other Bcl-2 family members, was rapidly up-regulated peaking at 4–8 h in human cervical cancer C33A cells. Supporting this observation, using anti-IL-6 or anti-IL-6 receptor antibody to interrupt the IL-6 autocrine loop in SiHa cells significantly reduced cellular level of Mcl-1. This study hypothesizes that the expression of Mcl-1 in cervical cancer cells is regulated by IL-6. The matter of which signaling pathways transduced by IL-6 is responsible for the Mcl-1 up-regulation is further investigated herein. Blocking the STAT3 or MAPK pathway with dominant-negative mutant STAT3F or the MEK inhibitor PD98059 failed to inhibit IL-6-mediated Mcl-1 expression. Meanwhile, the IL-6-induced Mcl-1 up-regulation was effectively abolished by treatment with PI 3-K inhibitors, LY294002. Additionally, overexpression of dominant-negative (dn) Akt in C33A cells could inhibit the IL-6-induced increase of Mcl-1. Finally, overexpression of IL-6 in C33A cells caused a markable resistance to apoptosis induced by doxorubicin or cisplatin. Transient transfection of IL-6-overexpressed cells with a mcl-1 antisense vector, leading to the attenuation of their apoptosis-resistant activity. In conclusion, the data herein suggest that IL-6 regulated the mcl-1 expression via a PI 3-K/Akt-dependent pathway that may facilitate the oncogenesis of human cervical cancer by modulating the apoptosis threshold. Oncogene (2001) 20, 5799–5809. [ABSTRACT FROM AUTHOR]

Studies the blast-wave interaction problem using both inviscid- and viscous-flow models. Initial conditions considered; Sketch of an initial blast-wave interaction with a flat plate; Blast-wave propagation in a free field.

Interleukin-6 (IL-6) is a pleitrophic cytokine that not only regulates growth and differentiation of many cell types, but also induces production of acute phase proteins (AAP) in hepatocytes. Our previous works have demonstrated that both PI 3-K/Akt and STAT3 pathways were concomitantly activated and cooperatively mediated the anti-apoptotic effect of IL-6. This investigation reports that IL-6 protected cells against apoptosis induced by a variety of agents including, TGF-β, UV and retinoic acid (RA) in Hep3B cells, suggesting that IL-6 is a fundamental determinant of hepatic cell survival. Mcl-1, but not other Bcl-2 family members, was rapidly up-regulated by IL-6, with a peak (approximately 3–4-fold) appearing at 4 h. Transient transfection of cells with a mcl-1 antisense vector, resulting in a 50–60% reduction of the anti-apoptotic effect of IL-6, indicating that Mcl-1 is a downstream effector of IL-6. Which signaling pathway transduced by IL-6 responsible for the Mcl-1 up-regulation was further investigated. In Hep3B cells, the JAK/STAT3, ERK, and PI 3-K/Akt pathways were activated by IL-6 stimulation. Blocking JAK/STAT3 activation with a dominant-negative mutant STAT3F or a JAK inhibitor AG490 could not influence IL-6-mediated Mcl-1 up-regulation. Similarly, PD98059 treatment, a MEK specific inhibitor, also failed to inhibit Mcl-1 expression. However, the IL-6-induced Mcl-1 up-regulation was effectively attenuated in the presence of PI 3-K inhibitors, LY294002 and wortmannin. Expression of dominant-negative Akt, but not Etk, could abrogate the IL-6-induced increase of Mcl-1. In conclusion, our results suggest that the anti-apoptotic effect of IL-6 is mediated, at least in part, by Mcl-1 expression and that is mainly through the PI 3-K/ Akt-dependent pathway. Oncogene (2001) 20, 677–685. [ABSTRACT FROM AUTHOR]

The healing of diabetic foot ulcers (DFUs) stalled in inflammation stage due to overabundance of inflammatory macrophages and the dysregulated M1/M2 macrophages in the lesion. Restoring the balance of M1/M2 macrophages plays a critical role in orchestrating the healing process of DFUs. By recognizing the therapeutic potential in M1/M2-macrophage-regulation for DFUs, we aim to evaluate the efficacy and safety of ON101, a topical new drug with M1/M2-macrophage-regulating mechanism versus a hydrocolloid dressing in an international, multicenter, randomized, controlled, evaluator-blind phase 3 study in 21 clinical/medical centers across the US, China, and Taiwan by following Guidance for Industry Chronic Cutaneous Ulcer and Burn Wounds — Developing Products for Treatment. 236 eligible patients with post-debrided DFU(s) between 1 - 25 cm2, present for ≥4 weeks and Wagner Grade 1 or 2, were randomized 1:1 to receive ON101 or comparator for up to 16 weeks followed by a 12-week follow-up. Baseline demography and medical history between the two groups were well balanced. The incidence of complete healing as the primary endpoint in full analysis set was 60.7% by ON101 and 35.1% by the comparator during the treatment period (p=0.0001). Time to complete ulcer healing as the secondary endpoint was noted faster in the ON101 group (p=0.002). No significant changes or differences between the two treatment groups in hematology, biochemistry (including HbA1c and fasting glucose), or vital signs. Related treatment of emergent adverse events was reported in 7 patients (5.7%) in the ON101 group and 5 (4.4%) from the comparator group. None of the serious adverse events was related to ON101 while there was a case of osteomyelitis reported to be related to the comparator. ON101, recently approved by Taiwan Food and Drug Administration, was shown with clinically significant efficacy and well-tolerated safety profile in DFUs which provides not only a new prospect in DFU management but a differentiated approach towards active-healing. Disclosure: M. Kuo: Employee; Self; Oneness Biotech Co., Ltd. [ABSTRACT FROM AUTHOR]

Background: Visual–perceptual defects in children can negatively affect their ability to perform activities of daily living. Conventional rehabilitation training for correcting visual–perceptual defects has limited training patterns and limited interactivity, which makes motivation difficult to sustain. Objective: We aimed to develop and evaluate an interactive digital game system for correcting visual–perceptual defects and evaluate its effectiveness. Methods: Participants were children aged 5 to 10 years with a diagnosis of visual–perceptual defect associated with a developmental disability. The children were randomized into a digital game group who received the traditional course of rehabilitation combined with an interactive digital game intervention (n=12) and a standard rehabilitation group (n=11) who only received the traditional course of rehabilitation. Each group underwent rehabilitation once a week for 4 weeks. Overall improvement in Test of Visual Perceptual Skills 3rd edition (TVPS-3) score and overall improvement in performance in the interactive digital game were evaluated. Parents and therapists were asked to complete a satisfaction questionnaire. Results: After 4 weeks, the TVPS-3 score had significantly increased (P=.002) in the digital game group (pre: mean 41.67, SD 13.88; post: 61.50, SD 21.64). In the standard rehabilitation group, the TVPS-3 score also increased, but the increase was not statistically significant (P=.58). Additionally, TVPS-3 score increases were significantly larger for the digital game group compared with those for the standard rehabilitation group (P=.005). Moreover, both parents and therapists were highly satisfied with the system. All 5 themes of satisfaction had mean scores higher than 4 in a 5-point scale questionnaire (mean 4.30, SD 0.56). Conclusions: The system has potential applications for improving visual–perceptual function in children undergoing medical rehabilitation for developmental disability [ABSTRACT FROM AUTHOR]

Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme responsible for DNA strand breaks, has been recently suggested to be crucial for apoptosis induced by a number chemotherapeutic drugs. In this study, we demonstrated that the PARP activity could be evidently elevated with a peak at 6 h when HL-60 cells were treated with a new anticancer drug GL331. Coincident with the peak of PARP activity, an apparent DNA fragmentation and apoptotic morphology were observed in cells treated with GL331. The subsequent apoptotic DNA fragmentation induced by GL331 could be completely blocked by transfecting cells with anti-sense PARP retroviral vector or by treating cells with PARP inhibitor, 3-aminobenzamide (3-AB). This blocking effect thus suggests that activation of PARP was critically involved in GL331-induced apoptosis. The fact that Bcl-2 has been found to antagonize cell death induced by a wide variety of agents, accounts for why we examined whether if Bcl-2 could antagonize GL331 effects. Interestingly, ectopic overexpression of Bcl-2 in either HL-60 or U937 cells caused in resistance towards GL331-elicited DNA fragmentation and cytotoxic effect. Additionally, Bcl-2 also attenuated the poly(ADP-ribosyl)ation of PARP itself as well as Histone H1 at the early period of drug treatment. However, Bcl-2 did not influence the extent of DNA strand breaks induced by GL331 in either control or Bcl-2-overexpressing cells. In addition, analysis of basal PARP activity in control and several Bcl-2 overexpressing clones revealed that Bcl-2 down-regulated PARP activity under the condition without DNA damages. Above findings suggest that poly(ADP-ribosyl)ation of nuclear targets is important for apoptosis induced by DNA-reactive anticancer drugs. [ABSTRACT FROM AUTHOR]

Brain injury often caused irreversible loss of neural tissue and resulted in serious neurological disability. Owing to the extreme complexity of the brain, it is still challenging to regenerate the brain tissue from injury and restore its normal function. Growth factors are critical signaling molecules that promote endogenous neural stem/progenitor cells (NSPCs) proliferation, migration and differentiation, resulting in functional brain recovery from injury. However, the labile nature of growth factor motivated us to develop advanced growth factor delivery strategies to precisely control over its release profile in vivo. In this review, we will discuss growth factor delivery via biomaterials for brain regeneration after injury. This review begins with an overview of some major forms of brain injury. The characteristic properties of growth factors are described to provide a biological basis for their use in the brain regeneration. The specific biomaterials that generally used for delivering growth factor to treat brain injury are also detailed summarized. In particular, we focus on an engineering strategy that promote endogenous repair by creating growth factor concentration gradients in vivo. The last part of the review introduces current challenges and perspectives for growth factor delivery via biomaterials. [ABSTRACT FROM AUTHOR]

Abstract: Dialkynylboron chlorides couple smoothly with aryl aldehydes at room temperature to afford 1,4-dialkynes in good to excellent yields. Dialkynylboron halides act simultaneously as Lewis acid and reactant in this coupling reaction. [Copyright &y& Elsevier]

Silicon nitride ceramics were prepared by spark plasma sintering (SPS) at temperatures of 1450°–1600°C for 3–12 min, using α-Si3N4 powders as raw materials and MgSiN2 as sintering additives. Almost full density of the sample was achieved after sintering at 1450°C for 6 min, while there was about 80 wt%α-Si3N4 phase left in the sintered material. α-Si3N4 was completely transformed to β-Si3N4 after sintering at 1500°C for 12 min. The thermal conductivity of sintered materials increased with increasing sintering temperature or holding time. Thermal conductivity of 100 W·(m·K)−1 was achieved after sintering at 1600°C for 12 min. The results imply that SPS is an effective and fast method to fabricate β-Si3N4 ceramics with high thermal conductivity when appropriate additives are used. [ABSTRACT FROM AUTHOR]

An alternate reaction mechanism for the boron tribromide mediated deprotection of aryl propargyl ethers based on the isolation of a key boron-containing byproduct is proposed. On the basis of the new mechanistic insight, we discovered that HBBr2·SMe2 can also be used for cleaving aryl propargyl ethers. [ABSTRACT FROM AUTHOR]